Maternal serum ADAM12s in the late first trimester of pregnancies with Trisomy 21

Abstract Background Patients with atypical values of HCG and/or PAPP-A are at higher risk of chromosomal abnormality and vascular complications of pregnancy. The performance of cfDNA in this particular population has not yet been evaluated. Objectives The primary objective was to evaluate the usefulness and reliability of cfDNA in screening for trisomy 21, 18 and 13 for patients with HCG < 0.25 multiple of median (MoM), HCG > 5.0 MoM and/or PAPP-A < 0.25 MoM, PAPP-A > 2.5 MoM. The secondary objective was to evaluate the contribution of cfDNA assay for the prediction of pregnancy’s vascular complications. Method Between June 2016 and July 2017, we analysed a women cohort from all over France who had at least one first trimester serum biomarker outside of normal range, in a retrospective, observational and multicentre study. Patients were included if they had a single pregnancy, normal first trimester ultrasound examination, whatever the result of the combined first trimester screening test was. The cfDNA was analysed by massive parallel sequencing technique. The accuracy of cfDNA assay was evaluated by calculation of sensitivity and specificity, and multivariate regression analysis was used to search for predictive factors for pregnancy’s vascular complications. Results Among the 498 patients who underwent a cfDNA assay in this context, twenty-one (4.2%) were excluded because of loss to follow-up. Out of 477, test failure occurred for four patients initially, reduced to two patients (0.4%) after redrawn. CfDNA was positive for Trisomy 21 (n = 19), Trisomy 18 (n = 6) and Trisomy 13 (n = 1) and negative in 449. The sensitivity of cfDNA assay for trisomy 21 screening was 100% (19/19) (IC 95% 82.4–100) and specificity 100% (458/458) (IC 95% 99.2–100). Among the 447 patients included for prediction of vascular complications, there were four cases of pregnancy induced hypertension and 10 cases of preeclampsia, for which no predictive factor was identified. Intra Uterine growth restriction under 5th percentile (n = 44, 9.8%) was significantly associated with a low fetal fraction (OR = 0.87, IC 95% 0.79–0.96, p = 0.006). Conclusion cfDNA assay is an effective and reliable tool for women with atypical profile of first trimester serum biomarkers.

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First Trimester Biochemical Screening for Trisomy 21: The Role of Free Beta hCG, Alpha Fetoprotein and Pregnancy Associated Plasma Protein A

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456329403100504 ◽

1994 ◽

Vol 31 (5) ◽

pp. 447-454 ◽

Cited By ~ 56

Author(s):

K Spencer ◽

D A Aitken ◽

J A Crossley ◽

G McCaw ◽

E Berry ◽

...

Keyword(s):

Chorionic Gonadotropin ◽

Plasma Protein ◽

Human Chorionic Gonadotropin ◽

Trisomy 21 ◽

False Positive Rate ◽

Protein A ◽

First Trimester ◽

Serum Markers ◽

Maternal Serum ◽

Detection Rates

The potential efficacy of screening for trisomy 21 in the first trimester, using maternal serum markers α fetoprotein, free β human chorionic gonadotropin, unconjugated oestriol and pregnancy associated plasma protein A, was studied in an unselected population of women between the seventh and fourteenth week of gestation. Using a combination of α fetoprotein and free β human chorionic gonadotropin, 53% of affected pregnancies could be identified at a false positive rate of 5%. Unconjugated oestriol and pregnancy associated plasma protein A levels were lower in cases of trisomy 21, but their inclusion with other markers did not significantly improve detection rate. Monitoring the same pregnancies also in the second trimester showed that screening in the first trimester identified the same cases as in the second. We conclude that first trimester screening using free β human chorionic gonadotropin and α fetoprotein, is a viable possibility and will lead to detection rates in excess of 50%. Prospective studies are needed to confirm these observations.

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